title: Toxic effects of tributyltin and its metabolites on harbour seal (Phoca vitulina) immune cells in vitro.
abstract: The widespread environmental contamination, bioaccumulation and endocrine disruptor effects of butyltins (BTs) to wildlife are well documented. Although suspected, potential effects of BTs exposure on the immune system of marine mammals have been little investigated. In this study, we assessed the effects of tributyltin (TBT) and its dealkylated metabolites dibutyltin (DBT) and monobutyltin (MBT) on the immune responses of harbour seals. Peripheral blood mononuclear cells isolated from pup and adult harbour seals were exposed in vitro to varying concentrations of BTs. DBT resulted in a significant decrease at 100 and 200 nM of phagocytotic activity and reduced significantly phagocytic efficiency at 200 nM in adult seals. There was no effect in phagocytosis with TBT and MBT. In pups, the highest concentration (200 nM) of DBT inhibited phagocytic efficiency. A reduction of tumor-killing capacity of adult natural killer (NK) cells occurred when leukocytes were incubated in vitro with 50 nM DBT and 200 nM TBT for 24h. In adult seals, T-lymphocyte proliferation was significantly suppressed when the cells were exposed to 200 nM TBT and 100 nM DBT. In pups, the proliferative response increased after an exposure to 100 nM TBT and 50 nM DBT, but decreased with 200 nM TBT and 100 nM DBT. The immune functions were more affected by BTs exposure in adults than in pups, suggesting that other unsuspected mechanisms could trigger immune parameters in pups. The toxic potential of BTs followed the order of DBT>TBT>MBT. BT concentrations of harbour seal pups from the St. Lawrence Estuary (Bic National Park) ranged between 0.1-0.4 ng Sn/g wet weight (ww) and 1.2-13.4 ng Sn/g ww in blood and blubber, respectively. For these animals, DBT concentrations were consistently below the quantification limit of 0.04 ng Sn/g ww in blood and 0.2 ng Sn/g ww in blubber. Results suggest that concentrations measured in pups are considered too low to induce toxic effects to their immune system during first days of life. However, based on our in vitro results, we hypothesize that BTs, and DBT in particular, could pose a serious threat to the immune functions in free-ranging harbour seal adults.
authors.affiliation: Institut National de Recherche Scientifique - Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada. heloise.frouin@iaf.inrs.ca
authors.forename: Héloïse
authors.initials: H
authors.lastname: Frouin
authors.forename: Michel
authors.initials: M
authors.lastname: Lebeuf
authors.forename: Richard
authors.initials: R
authors.lastname: Saint-Louis
authors.forename: Mike
authors.initials: M
authors.lastname: Hammill
authors.forename: Emilien
authors.initials: E
authors.lastname: Pelletier
authors.forename: Michel
authors.initials: M
authors.lastname: Fournier
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D005260:Female; D020128:Inhibitory Concentration 50; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D009947:Organotin Compounds / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects; D046049:Phoca / Q000276:immunology / Q000502:physiology*; D014220:Trialkyltin Compounds / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000097:blood / Q000378:metabolism / Q000633:toxicity*
chemical_list: D009947:Organotin Compounds; D014220:Trialkyltin Compounds; D014874:Water Pollutants, Chemical; C516409:mono-n-butyltin; C056189:di-n-butyltin; C011559:tributyltin